Clauss M, Weich H, Breier G, Knies U, Röckl W, Waltenberger J, Risau W
Abteilung für Molekulare Zellbiologie, Max-Planck-Institut für Physiologische und Klinische Forschung, D-61231 Bad Nauheim, Germany.
J Biol Chem. 1996 Jul 26;271(30):17629-34. doi: 10.1074/jbc.271.30.17629.
Two distinct receptors for vascular endothelial growth factor (VEGF), the tyrosine kinase receptors Flt-1 and Flk-1/KDR, have been described. In this study we show that monocytes, in contrast to endothelium, express only the VEGF receptor Flt-1, and that this receptor specifically binds also the VEGF homolog placenta growth factor (PlGF). Both VEGF and PlGF stimulate tissue factor production and chemotaxis in monocytes at equivalent doses. In contrast, endothelial cells expressing both the Flt-1 and the Flk-1/KDR receptors produce more tissue factor upon stimulation with VEGF than after stimulation with PlGF. Neutralizing antibodies to the KDR receptor reduce the VEGF-stimulated tissue factor induction in endothelial cells to levels obtained by stimulation with PlGF alone, but do not affect PlGF-induced tissue factor induction in endothelial cells nor the VEGF-dependent tissue factor production in monocytes. These findings strongly suggest Flt-1 as a functional receptor for VEGF and PlGF in monocytes and endothelial cells and identify this receptor as a mediator of monocyte recruitment and procoagulant activity.
已发现血管内皮生长因子（VEGF）有两种不同的受体，即酪氨酸激酶受体Flt-1和Flk-1/KDR。在本研究中，我们发现，与内皮细胞不同，单核细胞仅表达VEGF受体Flt-1，且该受体也能特异性结合VEGF同源物胎盘生长因子（PlGF）。VEGF和PlGF以等效剂量刺激单核细胞产生组织因子并引起趋化作用。相比之下，同时表达Flt-1和Flk-1/KDR受体的内皮细胞在受到VEGF刺激后比受到PlGF刺激后产生更多的组织因子。抗KDR受体的中和抗体可将VEGF刺激的内皮细胞中组织因子的诱导作用降低至仅用PlGF刺激所达到的水平，但不影响PlGF诱导的内皮细胞中组织因子的诱导作用，也不影响单核细胞中VEGF依赖性组织因子的产生。这些发现有力地表明Flt-1是单核细胞和内皮细胞中VEGF和PlGF的功能性受体，并确定该受体是单核细胞募集和促凝血活性的介质。
